PD-L1 Expression and Tumor-infiltrating Lymphocytes in Uterine Smooth Muscle Tumors: Implications for Immunotherapy

Elisheva Shanes, Lisa A. Friedman, Anne M. Mills*

*Corresponding author for this work

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

Immunotherapies targeting the PD-1/PD-L1 checkpoint axis are of growing interest for the treatment of mesenchymal neoplasms. However, PD-L1 expression and tumor-associated lymphocytes have not been well-investigated in uterine smooth muscle tumors. Forty-nine uterine smooth muscle tumors (23 leiomyosarcomas, 8 smooth muscle tumors of uncertain malignant potential [STUMP], 7 atypical leiomyomas, and 11 benign leiomyomas) were evaluated for tumoral and tumor-associated immune PD-L1 expression and tumor-associated T-cell infiltration. ALK immunohistochemistry was performed to exclude inflammatory myofibroblastic tumors. Tumor PD-L1 expression was seen in 70% of leiomyosarcomas and 14% of atypical leiomyomas; no cases of STUMP or benign leiomyoma demonstrated tumoral PD-L1. PD-L1 positivity was seen in tumor-associated immune cells in 78% of leiomyosarcomas, 25% of STUMP, no cases of atypical leiomyomas, and 9% of benign leiomyomas. Of the 23 leiomyosarcomas, 15 (65%) had a combined positive score ≥1, while of the 26 other uterine smooth muscle tumors, only 2 (8%) had a combined positive score ≥1. Tumor-associated CD8+ cells were highest among leiomyosarcomas (mean: 87/high-power fields vs. 17/high-power fields for nonleiomyosarcomas), and were significantly associated with PD-L1 expression. One PD-L1+, CD8-enriched leiomyosarcoma showed an ALK overexpression suggesting possible classification as inflammatory myofibroblastic tumor, but otherwise lacked morphologic features of this entity. Leiomyosarcomas demonstrate significantly higher PD-L1 expression and cytotoxic T-cell infiltration when compared with other uterine smooth muscle tumors. These data suggest the possibility that treatment with targeted immunotherapy may be appropriate in a selected population of patients with leiomyosarcoma and, potentially, in related tumors bearing ALK rearrangements.

Original languageEnglish (US)
Pages (from-to)792-801
Number of pages10
JournalAmerican Journal of Surgical Pathology
Volume43
Issue number6
DOIs
StatePublished - Jun 1 2019

Keywords

  • ALK
  • PD-L1
  • atypial leiomyoma
  • immunotherapy
  • inflammatory myofibroblastic tumor
  • leiomyosarcoma
  • smooth muscle tumor of uncertain significance
  • tumor-infiltrating lymphocytes
  • uterine smooth muscle tumor

ASJC Scopus subject areas

  • Anatomy
  • Surgery
  • Pathology and Forensic Medicine

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